THE ROLE OF ENZYME REGULATION IN METABOLISM 83 



regarding genetic control of gene action are in a state of rapid 

 development. 



The balance between inducer and repressor seems to provide a 

 flexible system for regulation of enzyme synthesis. The amount of 

 enzyme would depend on both the supply of substrate and the concen- 

 tration of end product present in the cell. Substrate would be utilized 

 at a high rate when available, but only when an excess of the end 

 product was not already present. 



If repression and induction functioned efficiently, one would an- 

 ticipate that the activities of the enzymes in vivo would be nearly as 

 fast as their maximum possible rates of action; i.e., the enzymes would 

 not be in large excess. Relatively few comparisons have been made be- 

 tween maximum activity in vitro and enzyme activity in vivo (con- 

 veniently measured by the rate of end product formation). Therefore 

 there is little to tell us how well such regulatory processes actually 

 function. Some data (Pardee, 1959) suggest that the enzymes of bio- 

 synthesis are often present in only a few times the minimum amount 

 that would be required for in vivo functioning if these enzymes op- 

 erated at full capacity. 



Repression is beneficial not only because it avoids the expenditure 

 of metabolites for formation of an unnecessary surplus of enzyme 

 molecules, but also because it prevents damage to the cells which can 

 occur when large amounts of certain enzymes are present. Excess alka- 

 line phosphatase, for instance, appears to be toxic to E. coli (Torriani, 

 1960). Theoretically almost any enzyme in excess should remove a 

 metabolite required for another pathway and thereby upset growth of 

 the cell. It is worth considering, too, that if more than about two dozen 

 enzymes were made in the amounts in which ^-galactosidase, alkaline 

 phosphatase, and aspartate transcarbamylase can be produced (5 per 

 cent each ) , a bacterium could not hold all of them. 



Feedback inhibition 



Induction-repression alone would not seem sufficient for regulation 

 of the rate of formation of small molecules, because processes control- 

 ling enzyme formation are slow compared to those involved in the syn- 

 thesis of small molecules. Let us suppose that repression is released for 

 a minute or so, and a ten-fold excess of an enzyme is formed. Even 

 though repression operates almost at once (Figure 2), and no more 

 enzyme is produced after repression is re-established, the enzyme al- 

 ready present would function at an excessive rate for more than three 

 generations, or until growth diluted it to the normal level. This situa- 

 tion could come about if the bacteria were subjected to some sudden 



